Excitatory and inhibitory effects of histamine on molluscan neurons.

Histamine elicited depolarization (excitation) in some neurons and hyperpolarization (inhibition) in other neurons of the central nervous system of the marine mollusc, Onchidium verruculatum. The histamine sensitive region was along the axon at some distance from the soma. H1-receptor blockers (SA-97 and mepyramine) suppressed the excitatory (H1) response without affecting the inhibitory (H2) response, while H2-receptor blockers (burimamide and metiamide) suppressed the H2-response without affecting the H1-response. The H1-response was associated with a marked increase in membrane conductance and was blocked by removal of the external Na. The H2-response consisted of a hyperpolarization without much change in conductance, compared with the hyperpolarization of same amplitude produced by glutamate in the same neuron. Passive polarization of the membrane and reduction of Cl concentrations to 1/5-1/25 caused no significant change in H2-response. The H2-response was slightly suppressed in K-free saline. Thus, it seems difficult to account for the hyperpolarization only by an increase in K or Cl conductance. Complete removal of Na and addition of ouabain blocked the H2-response, suggesting a contribution of an electrogenic Na-pump to the hyperpolarization. However, in 20 mM Na saline with or without K, histamine still caused clear hyperpolarization. In this solution, the histamine response was not affected by ouabain. Although it is difficult to exclude the possibility that an increase in K conductance may be responsible for the hyperpolarization, it is tentatively proposed as a hypothesis that the H2-response involved some active transport mechanism, different from a ouabain-sensitive electrogenic Na-pump.